Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes

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Authors: Jiwon Park ; Hangyul Song ; Shinje Moon ; Yumin Kim ; Sungsoo Cho ; Kyungdo Han ; Cheol-Young Park ; Sung Woo Cho ; Chang-Myung Oh

MeSH: Aged ; Animals ; Databases, Factual ; Diabetes Mellitus, Experimental / complications ; Diabetes Mellitus, Experimental / drug therapy ; Diabetic Cardiomyopathies* / drug therapy ; Diabetic Cardiomyopathies* / etiology ; Diabetic Cardiomyopathies* / prevention & control ; Female ; Fenofibrate* / pharmacology ; Fenofibrate* / therapeutic use ; Heart Failure* / drug therapy ; Hospitalization ; Humans ; Hypolipidemic Agents* / therapeutic use ; Inflammation Mediators / blood ; Inflammation Mediators / metabolism ; Male ; Mice, Inbred C57BL ; Middle Aged ; Myocardium / metabolism ; Myocardium / pathology ; Obesity* / drug therapy ; PPAR alpha / agonists ; PPAR alpha / metabolism ; Republic of Korea / epidemiology ; Risk Factors ; Signal Transduction / drug effects ; Time Factors ; Tumor Necrosis Factor-alpha / metabolism ; Ventricular Function, Left / drug effects

Abstract: Background: Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy.

Methods and results: We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate's beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824-0.998).

Conclusions: The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.